Extracts of the leaves, flowers, and gum of the tree Pterocarpus marsupium Roxb. (Leguminosae), also known as the Indian Kino Tree, have been used traditionally for the treatment of diarrhea, toothaches, fever and urinary and skin infections. Extracts of the bark have been long regarded as useful for the therapy of diabetes. Hypoglycemic activity of a naturally occurring pterostilbene, trans-1-(3,5-dimethoxyphenyl)-2-(4-hydroxyphenyl)-ethylene, isolated from the heartwood of pterocarpus marsupium as been reported by Manickam et al., J. Nat. Prod., 1997, 60:609-610. However, this pterostilbene is water insoluble and has not been shown to be efficacious in the treatment of diabetes, particularly in instances where insulin is present but inactive. The cause of diabetes is yet unknown, although both genetics and environment appear to be factors. Insulin dependent (Type I) and non-insulin dependent (Type II) are the types of diabetes. Type I is an autonomic immune disease in which the responsible autoantigen is still unknown. Patients of Type I need to take insulin intravenously to survive. However, Type II diabetes, the more common form of the disease, is a metabolic disorder resulting from the body's inability to make a sufficient amount of insulin or to properly use the insulin that is produced within the body. Insulin secretion and insulin resistance are considered the major defects, however, the precise genetic factors involved in the mechanism remain unknown.
Patients with diabetes usually have one or more of the following defects: less production of insulin by the pancreas; over secretion of glucose by the liver; impairment of glucose uptake by the skeletal muscle; defects in glucose transporters; desensitation of insulin receptors; and defects in the metabolic breakdown of polysaccharides. Other than the intravenous application of insulin, there are four classes of oral hypoglycemic agents in use.
Approved Mechanisms of Class Drugs Action Limitations sulfur urea 4 (1st acts on dev. of generation) pancreas to resistance and release more 2 (2nd insulin generation) biguanides metformin reduces liver glucose problems, secretion by lactic liver; acidosis improves insulin sensitivity alpha- acarbose interferes only useful glucosidase with at post- inhibitor digestive pradiandio process; level reduces glucose absorption thiazolidine troglipzone reduces "add-on" -dione insulin with resistancy insulin; not useful for people with heart and liver disease
As is apparent from the above table, each of the current agents available for use and treatment of diabetes has certain disadvantages. Accordingly, there is a continuing interest in the identification and development of new agents, particularly, water soluble agents which can be orally administered, for the use of treatment of diabetes.
Besides the pterostilbene discussed above, (-)-epicatechin, has also been isolated from pterocarpus marsupium by Sheehan et al., J. Nat. Prod., 1983, 46:232, and has been reported as having a hypoglycemic effect. See also Chakravarthy et al., Life Sciences, 1981, 29:2043-2047. Other phenolic type compounds have been isolated from pterocarpus marsupium by Maurya et al., J. Nat. Prod., 1984, 47:179-181; Jahromi et al., J. Nat. Prod., 1993, 56:989-994; and Maurya et al., Heterocycles, 1982, 19:2103-2107.